Interpretive Summary: Escherichia coli O157:H7 contains viruses that produce Shiga toxins, which are necessary to cause human disease. Previous work identified 16 groups of E. coli O157:H7 that differed on the locations where the Shiga toxin-containing viruses were inserted into the bacterial chromosome. Isolates from humans were predominately found in three of the groups, while 13 groups were found mostly among cattle isolates. This current work describes a broader study of the virus insertion sites in human and cattle isolates from different countries where E. coli O157:H7 is found and in U.S. isolates that represent the farm to food to patient continuum. This study demonstrated that the genetic groups of E. coli O157:H7 isolated from cattle in different countries differed. Although those countries with higher rates of a severe E. coli O157:H7-related disease (hemolytic uremic syndrome, HUS) tended to have a higher proportion of the three disease-associated groups in their cattle, this tendency was too weak to provide a satisfactory explanation for the differences in HUS incidence among countries.

Technical Abstract:
Enterohemorrhagic Escherichia coli O157:H7 (EHEC O157) is a major cause of bloody diarrhea and hemolytic uremic syndrome (HUS) worldwide, although the annual reported incidence of EHEC O157 associated HUS in various countries ranges forty-fold (0.01 to 0.41 cases per 100,000 population). Cattle are considered the principal reservoir of EHEC O157. With a variety of genotyping methods, some genotypes of EHEC O157 isolated from U.S. cattle are more frequently associated with human disease than others. We compared the genotype distribution of EHEC O157 in the cattle reservoir with human EHEC O157 disease incidence internationally to test the hypothesis that EHEC O157 disease incidence is due to differential exposure to genotypes of differing virulence. In this study, genotypes were defined by Shiga toxin-encoding bacteriophage insertion sites (Stx insertion genotypes). The correlation between Stx insertion site genotype distribution in cattle and HUS incidence for Australia, Japan, Korea, the U.S. and Scotland approached statistical significance (rs=0.87, P=0.054). The Stx insertion genotypes of clinical isolates from the U.S. and Australia differed (P=0.017), while those of isolates from Japan and Germany were intermediate. Isolates obtained along a putative transmission chain of U.S. cattle, ground beef and clinically ill humans in the U.S. each differed significantly in their distribution of Stx insertion genotypes (P less than 0.01). These disparities are consistent with differences in virulence, infectivity and/or environmental survival among EHEC O157 genotypes.